Inhibition by metoprolol of the antihypertensive effect of aspirin in young rats

RS Tuttle, V Banziger, S Patel and N Northrup

A group of 21-day-old, spontaneous hypertensive rats (SHR) received either aspirin (75-100 mg/kg), metoprolol (1.0-1.5 mg/kg) or both in their drinking water for 56 days. Controls received plain water. Groups of normotensive Wistar-Kyoto rats (WKY) received the same drug treatment as did the SHR. Blood pressure, heart rate and body weight were determined weekly, and water consumption was monitored on a daily basis. Renal prostaglandin (PG) activities were determined in a separate group of rats at 7 and at 56 days on each protocol. Blood pressures in the SHRs remained in the range of the WKY during 56 days of treatment with aspirin or metoprolol, but increased to hypertensive levels after exposure to plain water. Blood pressures in the WKY receiving aspirin or metoprolol were also lower than those receiving plain water, but the antihypertensive effect was somewhat slower in onset. The antihypertensive effects of aspirin and of metoprolol were lost in the SHR but not in the WKY when both drugs were given simultaneously in the drinking water. In comparison to rats receiving plain water, renal PG activity (PGF1 alpha and PGF2 alpha) was lower in rats receiving aspirin, metoprolol or both together. The mechanism for the antihypertensive effect of aspirin in the young SHR may be related to a decline in renal PG content, or to the release of other hormones controlling water and electrolyte balance. Reports that the cyclooxygenase inhibitors, such as aspirin, can block the antihypertensive effect of the beta adrenoceptor antagonists is confirmed in chronic studies using the SHR model.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 234, Issue 1, pp. 166-171, 07/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics